Early detection of high-grade tubal serous carcinoma in women at low risk for hereditary breast and ovarian cancer syndrome by systematic examination of fallopian tubes incidentally removed during benign surgery

Am J Surg Pathol. 2014 Jun;38(6):729-42. doi: 10.1097/PAS.0000000000000199.

Abstract

Early detection of sporadic pelvic serous carcinoma remains an elusive goal. In women at high risk for hereditary breast and ovarian cancer syndrome who undergo prophylactic salpingectomy, systematic pathologic examination of the fallopian tubes will detect occult tubal cancer, mostly in the fimbriae, of a minority of women. Such tubal cancers are the putative precursor to advanced-stage pelvic cancer. We hypothesized that early tubal cancer detection can also be accomplished in women at low risk using a similar approach. In this study, we performed complete and systematic examination of the fallopian tubes removed during surgery performed for benign indications. Among 522 women, 4 cases of serous tubal intraepithelial carcinoma (STIC) were identified. Three of these cases would have gone undetected using the current standard of care of sampling only a single random section of the tube. The fourth case was accompanied by occult ovarian carcinoma. The fimbriae contained STIC in 3 of the 4 cases and atypical mucosa in 1 case in which the STIC was in the nonfimbriated portion of the tube. The morphologic and immunohistochemical features (aberrant p53 and MIB-1) of these STICs were similar to those expected in high-risk women. All 4 patients with STIC underwent BRCA1 and BRCA2 gene testing; no germline mutations were identified in any patient. An additional 11 specimens contained atypical mucosal proliferations that fell short of morphologic and immunohistochemical criteria for STIC. Two of these 11 fulfilled criteria for a serous tubal intraepithelial lesion, and the remaining atypical proliferations exhibited normal p53 and MIB-1. For most specimens, the fimbriae could be completely submitted in 1 or 2 cassettes per tube. These results demonstrate that systematic examination of the tubal fimbriae can serve as a form of early detection of sporadic tubal cancer without incurring significant labor or cost. We propose that the tubal fimbriae should be completely examined in all patients undergoing benign surgery even if there are no clinical features to suggest risk for hereditary breast and ovarian cancer syndrome.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Carcinoma in Situ / chemistry
  • Carcinoma in Situ / pathology*
  • Cell Proliferation
  • DNA Mutational Analysis
  • Early Detection of Cancer*
  • Fallopian Tube Neoplasms / chemistry
  • Fallopian Tube Neoplasms / pathology*
  • Fallopian Tubes / chemistry
  • Fallopian Tubes / pathology*
  • Fallopian Tubes / surgery
  • Female
  • Hereditary Breast and Ovarian Cancer Syndrome / genetics*
  • Humans
  • Immunohistochemistry
  • Incidental Findings*
  • Ki-67 Antigen / analysis
  • Middle Aged
  • Mutation*
  • Neoplasm Grading
  • Neoplasms, Cystic, Mucinous, and Serous / chemistry
  • Neoplasms, Cystic, Mucinous, and Serous / pathology*
  • Predictive Value of Tests
  • Prospective Studies
  • Risk Factors
  • Salpingectomy
  • Tumor Suppressor Protein p53 / analysis
  • Young Adult

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Biomarkers, Tumor
  • Ki-67 Antigen
  • TP53 protein, human
  • Tumor Suppressor Protein p53